Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment

Abstract

A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

The invention claimed is: 
     
       1. A pharmaceutical composition comprising a therapeutically effective amount of a mini-gastrin analogue having the formula:
   X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 , 
 
       wherein Y is norleucine and X is a chemical group attached to the peptide for the purpose of therapeutic intervention at CCK-2 receptor associated diseases, and a pharmaceutically acceptable carrier. 
     
     
       2. The pharmaceutical composition of  claim 1 , wherein the therapeutically effective amount is effective for treating CCK-2 receptor positive tumors. 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein the CCK-2 receptor positive tumor is selected from the group consisting of medullary thyroid carcinomas (MTC), small cell lung cancers (SCLC), astrocytomes and stromal ovarial tumors. 
     
     
       4. The pharmaceutical composition of  claim 1 , wherein X is a chelator for radiometals complexed with a radionuclide. 
     
     
       5. The pharmaceutical composition of  claim 4 , wherein the chelator for radiometals is DOTA. 
     
     
       6. The pharmaceutical composition of  claim 4 , wherein the radionuclide is selected from the group consisting of  177 Lu,  90 Y and  111 In. 
     
     
       7. The pharmaceutical composition of  claim 5 , wherein the mini-gastrin analogue is labelled with  177 Lu. 
     
     
       8. The pharmaceutical composition of  claim 1 , wherein X is an optically active chemical compound. 
     
     
       9. The pharmaceutical composition of  claim 1 , wherein X is a chemotherapeutic active compound. 
     
     
       10. The pharmaceutical composition of  claim 1 , wherein X is a nanoparticle or liposome which has a therapeutic function by itself or which is loaded with an active compound. 
     
     
       11. The pharmaceutical composition of  claim 10 , wherein X is a nanoparticle or liposome which is an optically active agent. 
     
     
       12. The pharmaceutical composition of  claim 1 , which is formulated for i.v. injection. 
     
     
       13. The pharmaceutical composition of  claim 7 , wherein the isotope:peptide ratio is 1:47. 
     
     
       14. The pharmaceutical composition of  claim 5 , wherein the radionuclide is selected from the group consisting of  177 Lu,  90 Y and  111 In.